Dataset Information

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

ABSTRACT:

Importance

The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.

Objective

To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.

Design, setting, and participants

This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up.

Interventions

Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings).

Main outcomes and measures

The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects.

Results

Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively).

Conclusions and relevance

In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes.

Trial registration

Clinicaltrials.gov Identifier: NCT03210103.

SUBMITTER: Palma DA

PROVIDER: S-EPMC9052108 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Palma David A DA Prisman Eitan E Berthelet Eric E Tran Eric E Hamilton Sarah S Wu Jonn J Eskander Antoine A Higgins Kevin K Karam Irene I Poon Ian I Husain Zain Z Enepekides Danny D Hier Michael M Sultanem Khalil K Richardson Keith K Mlynarek Alex A Johnson-Obaseki Stephanie S Odell Michael M Bayley Andrew A Dowthwaite Samuel S Jackson James E JE Dzienis Marcin M O'Neil John J Chandarana Shamir S Banerjee Robyn R Hart Robert R Chung Jeffson J Tenenholtz Todd T Krishnan Suren S Le Hien H Yoo John J Mendez Adrian A Winquist Eric E Kuruvilla Sara S Stewart Paul P Warner Andrew A Mitchell Sylvia S Chen Jeff J Parker Christina C Wehrli Bret B Kwan Keith K Theurer Julie J Sathya Jinka J Hammond J Alex JA Read Nancy N Venkatesan Varagur V MacNeil S Danielle SD Fung Kevin K Nichols Anthony C AC

JAMA oncology 20220601 6

<h4>Importance</h4>The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown.<h4>Objective</h4>To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC.<h4>Design, setting, and participants</h4>This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic canc ...[more]

PMID: 35482348

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Project description:ImportanceDefinitive radiotherapy (RT) and primary surgery (PS) are considered to be equally viable local therapy modalities for oropharyngeal squamous cell carcinoma (OPSCC). The comparative effectiveness of these therapies is often debated, and treatment decisions are based on a paucity of comparative data.ObjectiveTo examine the differences in overall survival and key toxic effects in patients with OPSCC treated with RT and PS.Design, setting, and participantsThis retrospective cohort analysis used the HealthCore Integrated Research Database to identify 884 patients diagnosed with OPSCC from January 1, 2007, to December 31, 2014. Patients were categorized as receiving definitive RT (with or without chemotherapy) or PS (with or without adjuvant RT or chemoradiotherapy). Administrative claims data were linked with state cancer registries from California, Connecticut, Georgia, Kentucky, New York, and Ohio. Data analysis was performed from February 29, 2016, to February 6, 2018.ExposuresDefinitive RT or PS.Main outcomes and measuresOverall survival was analyzed using Cox proportional hazards regression. Risks of gastrostomy dependence, esophageal stricture, and osteoradionecrosis were determined through claims and analyzed using logistic regression.ResultsA total of 884 patients (608 [68.8%] in the RT group and 276 [31.2%] in the PS group; mean [SD] age, 61.5 [10.7] years; 727 [82.2%] male; 842 [95.3%] white) were included in this study. The 3-year overall survival was 76% among patients treated with RT and 81% among patients treated with PS (hazard ratio, 0.76; 95% CI, 0.54-1.01). On multivariable analysis, increasing age, female sex, and low income were associated with inferior survival; treatment type was not. Patients treated with RT were more likely to have gastrostomy dependence within the first year (391 [64.3%] vs 127 [46.0%]; adjusted OR, 0.57; 95% CI, 0.42-0.77). After treating chemotherapy as an effect modifier, there was no difference between modalities. Treatment type was not associated with esophageal stricture or osteoradionecrosis risk. Mean costs were approximately $100 000 for payers and $5000 for patients, with no adjusted differences between RT and PS.Conclusions and relevanceThis study suggests that RT and PS are equally viable treatment options for OPSCC; therefore, local therapy decisions may be individualized to each patient. However, the frequent addition of chemotherapy was associated with increased gastrostomy dependence among patients undergoing RT, which may be relevant in clinical decision making.

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Dataset Information

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

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